title: Ketamine depresses toll-like receptor 3 signaling in spinal microglia in a rat model of neuropathic pain.
abstract: Reports suggest that microglia play a key role in spinal nerve ligation (SNL)-induced neuropathic pain, and toll-like receptor 3 (TLR3) has a substantial role in the activation of spinal microglia and the development of tactile allodynia after nerve injury. In addition, ketamine application could suppress microglial activation in vitro, and ketamine could inhibit proinflammatory gene expression possibly by suppressing TLR-mediated signal transduction. Therefore, the present study was designed to disclose whether intrathecal ketamine could suppress SNL-induced spinal microglial activation and exert some antiallodynic effects on neuropathic pain by suppressing TLR3 activation. Behavioral results showed that intrathecal ketamine attenuated SNL-induced mechanical allodynia, as well as spinal microglial activation, in a dose-dependent manner. Furthermore, Western blot analysis displayed that ketamine application downregulated SNL-induced phosphorylated-p38 (p-p38) expression, which was specifically expressed in spinal microglia but not in astrocytes or neurons. Besides, ketamine could reverse TLR3 agonist (polyinosine-polycytidylic acid)-induced mechanical allodynia and spinal microglia activation. It was concluded that intrathecal ketamine depresses TLR3-induced spinal microglial p-p38 mitogen-activated protein kinase pathway activation after SNL, probably contributing to the antiallodynic effect of ketamine on SNL-induced neuropathic pain.
authors.affiliation: Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Mei
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Li-Xian
authors.initials: LX
authors.lastname: Xu
authors.forename: Yun-Qing
authors.initials: YQ
authors.lastname: Li
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007839:Functional Laterality; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009437:Neuralgia / Q000150:complications / Q000473:pathology*; D010147:Pain Measurement / Q000379:methods; D011070:Poly I-C / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013116:Spinal Cord / Q000473:pathology*; D016708:Synaptophysin / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism*
chemical_list: D000700:Analgesics; D039481:CD11b Antigen; D009419:Nerve Tissue Proteins; D016708:Synaptophysin; C530472:TLR3 protein, rat; D051196:Toll-Like Receptor 3; D007649:Ketamine; D011070:Poly I-C